Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

DNA excision repair protein ERCC-8

Gene

ERCC8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Substrate-recognition component of the CSA complex, a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex, involved in transcription-coupled nucleotide excision repair. The CSA complex (DCX(ERCC8) complex) promotes the ubiquitination and subsequent proteasomal degradation of ERCC6 in a UV-dependent manner; ERCC6 degradation is essential for the recovery of RNA synthesis after transcription-coupled repair. It is required for the recruitment of XAB2, HMGN1 and TCEA1/TFIIS to a transcription-coupled repair complex which removes RNA polymerase II-blocking lesions from the transcribed strand of active genes.3 Publications

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

GO - Molecular functioni

  • protein complex binding Source: UniProtKB

GO - Biological processi

  • cellular response to DNA damage stimulus Source: UniProtKB
  • nucleotide-excision repair Source: UniProtKB
  • positive regulation of DNA repair Source: UniProtKB
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
  • protein autoubiquitination Source: UniProtKB
  • protein polyubiquitination Source: UniProtKB
  • response to oxidative stress Source: UniProtKB
  • response to UV Source: UniProtKB
  • response to X-ray Source: Ensembl
  • transcription-coupled nucleotide-excision repair Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

DNA damage, DNA repair, Ubl conjugation pathway

Enzyme and pathway databases

BioCyciZFISH:ENSG00000049167-MONOMER.
ReactomeiR-HSA-6781823. Formation of TC-NER Pre-Incision Complex.
R-HSA-6781827. Transcription-Coupled Nucleotide Excision Repair (TC-NER).
R-HSA-6782135. Dual incision in TC-NER.
R-HSA-6782210. Gap-filling DNA repair synthesis and ligation in TC-NER.
SignaLinkiQ13216.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
DNA excision repair protein ERCC-8
Alternative name(s):
Cockayne syndrome WD repeat protein CSA
Gene namesi
Name:ERCC8
Synonyms:CKN1, CSA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:3439. ERCC8.

Subcellular locationi

GO - Cellular componenti

  • Cul4A-RING E3 ubiquitin ligase complex Source: UniProtKB
  • nuclear matrix Source: MGI
  • nucleoplasm Source: Reactome
  • nucleotide-excision repair complex Source: MGI
  • nucleus Source: MGI
  • protein complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Cockayne syndrome A (CSA)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare disorder characterized by cutaneous sensitivity to sunlight, abnormal and slow growth, cachectic dwarfism, progeroid appearance, progressive pigmentary retinopathy and sensorineural deafness. There is delayed neural development and severe progressive neurologic degeneration resulting in mental retardation. Two clinical forms are recognized: in the classical form or Cockayne syndrome type 1, the symptoms are progressive and typically become apparent within the first few years or life; the less common Cockayne syndrome type 2 is characterized by more severe symptoms that manifest prenatally. Cockayne syndrome shows some overlap with certain forms of xeroderma pigmentosum. Unlike xeroderma pigmentosum, patients with Cockayne syndrome do not manifest increased freckling and other pigmentation abnormalities in the skin and have no significant increase in skin cancer.
See also OMIM:216400
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_063507160A → T in CSA. 1 PublicationCorresponds to variant rs281875222dbSNPEnsembl.1
Natural variantiVAR_025380160A → V in CSA. 1 PublicationCorresponds to variant rs121434325dbSNPEnsembl.1
Natural variantiVAR_063508194W → C in CSA. 1 PublicationCorresponds to variant rs281875223dbSNPEnsembl.1
Natural variantiVAR_063509202L → S in CSA. 1 PublicationCorresponds to variant rs281875224dbSNPEnsembl.1
Natural variantiVAR_025381205A → P in CSA. 1 PublicationCorresponds to variant rs121434326dbSNPEnsembl.1
Natural variantiVAR_063510266D → G in CSA. 1 PublicationCorresponds to variant rs281875225dbSNPEnsembl.1
UV-sensitive syndrome 2 (UVSS2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive disorder characterized by cutaneous photosensitivity and mild freckling in the absence of neurological abnormalities or skin tumors.
See also OMIM:614621
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_068177361W → C in UVSS2. 1 PublicationCorresponds to variant rs281875221dbSNPEnsembl.1

Keywords - Diseasei

Cockayne syndrome, Deafness, Disease mutation, Dwarfism

Organism-specific databases

DisGeNETi1161.
MalaCardsiERCC8.
MIMi216400. phenotype.
614621. phenotype.
OpenTargetsiENSG00000049167.
Orphaneti90321. Cockayne syndrome type 1.
90322. Cockayne syndrome type 2.
90324. Cockayne syndrome type 3.
178338. UV-sensitive syndrome.
PharmGKBiPA27853.

Polymorphism and mutation databases

BioMutaiERCC8.
DMDMi3121917.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000509701 – 396DNA excision repair protein ERCC-8Add BLAST396

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei390PhosphoserineCombined sources1
Modified residuei391PhosphoserineCombined sources1
Modified residuei392PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ13216.
MaxQBiQ13216.
PaxDbiQ13216.
PeptideAtlasiQ13216.
PRIDEiQ13216.

PTM databases

iPTMnetiQ13216.
PhosphoSitePlusiQ13216.

Expressioni

Gene expression databases

BgeeiENSG00000049167.
CleanExiHS_ERCC8.
ExpressionAtlasiQ13216. baseline and differential.
GenevisibleiQ13216. HS.

Organism-specific databases

HPAiCAB010750.

Interactioni

Subunit structurei

Part of the CSA complex (DCX(ERCC8) complex), a DCX E3 ubiquitin-protein ligase complex containing ERCC8, RBX1, DDB1 and CUL4A; the CSA complex interacts with RNA polymerase II; upon UV irradiation it interacts with the COP9 signalosome and preferentially with the hyperphosphorylated form of RNA polymerase II. Interacts with ERCC6 and KIAA1530/UVSSA. Interacts with a subunit of RNA polymerase II TFIIH. Interacts directly with DDB1 (PubMed:22118460).4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ERCC6Q034682EBI-596556,EBI-295284
XAB2Q9HCS73EBI-295260,EBI-295232

GO - Molecular functioni

  • protein complex binding Source: UniProtKB

Protein-protein interaction databases

BioGridi107581. 42 interactors.
DIPiDIP-291N.
IntActiQ13216. 10 interactors.
MINTiMINT-1417899.
STRINGi9606.ENSP00000265038.

Structurei

Secondary structure

1396
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi2 – 10Combined sources9
Helixi15 – 28Combined sources14
Beta strandi30 – 32Combined sources3
Beta strandi36 – 38Combined sources3
Beta strandi46 – 51Combined sources6
Turni53 – 55Combined sources3
Beta strandi58 – 63Combined sources6
Beta strandi68 – 72Combined sources5
Beta strandi77 – 80Combined sources4
Beta strandi82 – 84Combined sources3
Beta strandi86 – 90Combined sources5
Beta strandi102 – 107Combined sources6
Beta strandi115 – 119Combined sources5
Beta strandi122 – 128Combined sources7
Turni129 – 132Combined sources4
Beta strandi133 – 139Combined sources7
Beta strandi144 – 149Combined sources6
Beta strandi158 – 176Combined sources19
Beta strandi180 – 182Combined sources3
Beta strandi189 – 194Combined sources6
Beta strandi201 – 206Combined sources6
Beta strandi211 – 215Combined sources5
Beta strandi223 – 225Combined sources3
Turni228 – 231Combined sources4
Turni237 – 239Combined sources3
Beta strandi248 – 253Combined sources6
Beta strandi257 – 264Combined sources8
Beta strandi269 – 273Combined sources5
Turni274 – 276Combined sources3
Beta strandi302 – 305Combined sources4
Beta strandi307 – 312Combined sources6
Beta strandi315 – 320Combined sources6
Turni321 – 323Combined sources3
Beta strandi326 – 330Combined sources5
Beta strandi337 – 343Combined sources7
Turni344 – 347Combined sources4
Beta strandi348 – 353Combined sources6
Beta strandi358 – 363Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4A11X-ray3.31B1-396[»]
ProteinModelPortaliQ13216.
SMRiQ13216.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati33 – 73WD 1Add BLAST41
Repeati88 – 129WD 2Add BLAST42
Repeati133 – 173WD 3Add BLAST41
Repeati177 – 216WD 4Add BLAST40
Repeati235 – 274WD 5Add BLAST40
Repeati281 – 321WD 6Add BLAST41
Repeati325 – 363WD 7Add BLAST39

Sequence similaritiesi

Contains 7 WD repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG4283. Eukaryota.
ENOG410Z0MQ. LUCA.
GeneTreeiENSGT00390000009065.
HOGENOMiHOG000248233.
HOVERGENiHBG005409.
InParanoidiQ13216.
KOiK10570.
OMAiGHYNNVD.
OrthoDBiEOG091G09HW.
PhylomeDBiQ13216.
TreeFamiTF101237.

Family and domain databases

Gene3Di2.130.10.10. 1 hit.
InterProiIPR020472. G-protein_beta_WD-40_rep.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamiPF00400. WD40. 4 hits.
[Graphical view]
PRINTSiPR00320. GPROTEINBRPT.
SMARTiSM00320. WD40. 5 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 1 hit.
PROSITEiPS00678. WD_REPEATS_1. 2 hits.
PS50082. WD_REPEATS_2. 5 hits.
PS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q13216-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MLGFLSARQT GLEDPLRLRR AESTRRVLGL ELNKDRDVER IHGGGINTLD
60 70 80 90 100
IEPVEGRYML SGGSDGVIVL YDLENSSRQS YYTCKAVCSI GRDHPDVHRY
110 120 130 140 150
SVETVQWYPH DTGMFTSSSF DKTLKVWDTN TLQTADVFNF EETVYSHHMS
160 170 180 190 200
PVSTKHCLVA VGTRGPKVQL CDLKSGSCSH ILQGHRQEIL AVSWSPRYDY
210 220 230 240 250
ILATASADSR VKLWDVRRAS GCLITLDQHN GKKSQAVESA NTAHNGKVNG
260 270 280 290 300
LCFTSDGLHL LTVGTDNRMR LWNSSNGENT LVNYGKVCNN SKKGLKFTVS
310 320 330 340 350
CGCSSEFVFV PYGSTIAVYT VYSGEQITML KGHYKTVDCC VFQSNFQELY
360 370 380 390
SGSRDCNILA WVPSLYEPVP DDDETTTKSQ LNPAFEDAWS SSDEEG
Length:396
Mass (Da):44,055
Last modified:November 1, 1996 - v1
Checksum:iEC962D56226D717B
GO
Isoform 2 (identifier: Q13216-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     185-205: HRQEILAVSWSPRYDYILATA → IFILFQTATTLSKRFNKKKRY
     206-396: Missing.

Note: No experimental confirmation available.
Show »
Length:205
Mass (Da):23,182
Checksum:i6553CE607A392576
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_053392150S → C.Corresponds to variant rs167037dbSNPEnsembl.1
Natural variantiVAR_063507160A → T in CSA. 1 PublicationCorresponds to variant rs281875222dbSNPEnsembl.1
Natural variantiVAR_025380160A → V in CSA. 1 PublicationCorresponds to variant rs121434325dbSNPEnsembl.1
Natural variantiVAR_063508194W → C in CSA. 1 PublicationCorresponds to variant rs281875223dbSNPEnsembl.1
Natural variantiVAR_016319200Y → C.1 PublicationCorresponds to variant rs4647105dbSNPEnsembl.1
Natural variantiVAR_063509202L → S in CSA. 1 PublicationCorresponds to variant rs281875224dbSNPEnsembl.1
Natural variantiVAR_025381205A → P in CSA. 1 PublicationCorresponds to variant rs121434326dbSNPEnsembl.1
Natural variantiVAR_063510266D → G in CSA. 1 PublicationCorresponds to variant rs281875225dbSNPEnsembl.1
Natural variantiVAR_068177361W → C in UVSS2. 1 PublicationCorresponds to variant rs281875221dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_013914185 – 205HRQEI…ILATA → IFILFQTATTLSKRFNKKKR Y in isoform 2. 1 PublicationAdd BLAST21
Alternative sequenceiVSP_013915206 – 396Missing in isoform 2. 1 PublicationAdd BLAST191

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U28413 mRNA. Translation: AAA82605.1.
CR536563 mRNA. Translation: CAG38800.1.
BT020021 mRNA. Translation: AAV38824.1.
AY213194 Genomic DNA. Translation: AAO21128.1.
AK314511 mRNA. Translation: BAG37111.1.
CH471123 Genomic DNA. Translation: EAW55004.1.
BC009793 mRNA. Translation: AAH09793.1.
CCDSiCCDS3978.1. [Q13216-1]
PIRiA57090.
RefSeqiNP_000073.1. NM_000082.3. [Q13216-1]
NP_001007235.1. NM_001007234.2. [Q13216-2]
UniGeneiHs.435237.

Genome annotation databases

EnsembliENST00000265038; ENSP00000265038; ENSG00000049167. [Q13216-1]
GeneIDi1161.
KEGGihsa:1161.
UCSCiuc003jsm.4. human. [Q13216-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Allelic variations of the XP genes
Atlas of Genetics and Cytogenetics in Oncology and Haematology
NIEHS-SNPs
Mendelian genes excision repair cross-complementing rodent repair deficiency, complementation group 8 (ERCC8)

Leiden Open Variation Database (LOVD)

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U28413 mRNA. Translation: AAA82605.1.
CR536563 mRNA. Translation: CAG38800.1.
BT020021 mRNA. Translation: AAV38824.1.
AY213194 Genomic DNA. Translation: AAO21128.1.
AK314511 mRNA. Translation: BAG37111.1.
CH471123 Genomic DNA. Translation: EAW55004.1.
BC009793 mRNA. Translation: AAH09793.1.
CCDSiCCDS3978.1. [Q13216-1]
PIRiA57090.
RefSeqiNP_000073.1. NM_000082.3. [Q13216-1]
NP_001007235.1. NM_001007234.2. [Q13216-2]
UniGeneiHs.435237.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4A11X-ray3.31B1-396[»]
ProteinModelPortaliQ13216.
SMRiQ13216.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107581. 42 interactors.
DIPiDIP-291N.
IntActiQ13216. 10 interactors.
MINTiMINT-1417899.
STRINGi9606.ENSP00000265038.

PTM databases

iPTMnetiQ13216.
PhosphoSitePlusiQ13216.

Polymorphism and mutation databases

BioMutaiERCC8.
DMDMi3121917.

Proteomic databases

EPDiQ13216.
MaxQBiQ13216.
PaxDbiQ13216.
PeptideAtlasiQ13216.
PRIDEiQ13216.

Protocols and materials databases

DNASUi1161.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265038; ENSP00000265038; ENSG00000049167. [Q13216-1]
GeneIDi1161.
KEGGihsa:1161.
UCSCiuc003jsm.4. human. [Q13216-1]

Organism-specific databases

CTDi1161.
DisGeNETi1161.
GeneCardsiERCC8.
GeneReviewsiERCC8.
H-InvDBHIX0004887.
HGNCiHGNC:3439. ERCC8.
HPAiCAB010750.
MalaCardsiERCC8.
MIMi216400. phenotype.
609412. gene.
614621. phenotype.
neXtProtiNX_Q13216.
OpenTargetsiENSG00000049167.
Orphaneti90321. Cockayne syndrome type 1.
90322. Cockayne syndrome type 2.
90324. Cockayne syndrome type 3.
178338. UV-sensitive syndrome.
PharmGKBiPA27853.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4283. Eukaryota.
ENOG410Z0MQ. LUCA.
GeneTreeiENSGT00390000009065.
HOGENOMiHOG000248233.
HOVERGENiHBG005409.
InParanoidiQ13216.
KOiK10570.
OMAiGHYNNVD.
OrthoDBiEOG091G09HW.
PhylomeDBiQ13216.
TreeFamiTF101237.

Enzyme and pathway databases

UniPathwayiUPA00143.
BioCyciZFISH:ENSG00000049167-MONOMER.
ReactomeiR-HSA-6781823. Formation of TC-NER Pre-Incision Complex.
R-HSA-6781827. Transcription-Coupled Nucleotide Excision Repair (TC-NER).
R-HSA-6782135. Dual incision in TC-NER.
R-HSA-6782210. Gap-filling DNA repair synthesis and ligation in TC-NER.
SignaLinkiQ13216.

Miscellaneous databases

GeneWikiiERCC8_(gene).
GenomeRNAii1161.
PROiQ13216.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000049167.
CleanExiHS_ERCC8.
ExpressionAtlasiQ13216. baseline and differential.
GenevisibleiQ13216. HS.

Family and domain databases

Gene3Di2.130.10.10. 1 hit.
InterProiIPR020472. G-protein_beta_WD-40_rep.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
[Graphical view]
PfamiPF00400. WD40. 4 hits.
[Graphical view]
PRINTSiPR00320. GPROTEINBRPT.
SMARTiSM00320. WD40. 5 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 1 hit.
PROSITEiPS00678. WD_REPEATS_1. 2 hits.
PS50082. WD_REPEATS_2. 5 hits.
PS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiERCC8_HUMAN
AccessioniPrimary (citable) accession number: Q13216
Secondary accession number(s): B2RB64, Q6FHX5, Q96GB9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: November 1, 1996
Last modified: November 2, 2016
This is version 163 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.